Pericentromeric satellite repeat expansions through RNA-derived DNA intermediates in cancer
Abstract
Unique among the large number of noncoding RNA species, the pericentromeric human satellite II (HSATII) repeat is massively expressed in a broad set of epithelial cancers but is nearly undetectable in normal tissues. Here, we show that deregulation of HSATII expression is tightly linked to growth under nonadherent conditions, and we uncover an unexpected mechanism by which HSATII RNA-derived DNA (rdDNA) leads to progressive elongation of pericentromeric regions in tumors. The remarkable specificity of HSATII overexpression in cancers, together with the consequences of targeting its RT, points to a potential novel vulnerability of cancer cells.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 02, 2015
- Source ID
- 10.1073/pnas.1518008112
Entities
People
- Andrew W. Xu
- Ben S. Wittner
- Brian W. Brannigan
- Daniel Haber
- David T Ting
- Eunjung Lee
- Francesca Bersani
- Hyunchul Jung
- Kristina Xega
- Mingzhu Liu
- Olivia C. Mackenzie
- Peter J. Park
- Peter V. Kharchenko
- Shyamala Maheswaran
- Sridhar Ramaswamy
Organizations
- Boston Children's Hospital
- Brigham and Women's Hospital
- Burroughs Wellcome Fund
- Harvard Medical School
- Howard Hughes Medical Institute
- Massachusetts General Hospital
- National Cancer Institute
- National Foundation for Cancer Research
- Samsung Medical Center
- Susan G. Komen for the Cure
- United States Department of Defense